We will examine the biochemical and genetic factors that determine the level of resistance of Neisseria gonorrhoeae to the oxygen independent antimicrobial systems of the human PMN. We will purify antimicrobial proteins from PMN granule extracts by sequential ion-exchange and molecular-sieve chromatography. Purified proteins will be tested for antimicrobial activity against isogenic strains that contain defined mutations which affect cell envelope structure. Genetic derivatives that exhibit increased resistance or sensitivity to granule proteins will be isolated and analyzed for alterations in outer membrane proteins and lipopolysaccharide. These mutants will then be used to construct isogenic pairs that differ in resistance to granule proteins. This information will allow us to define those cell surface structures involved in determining the resistance of the gonococcus to the oxygen independent microbiocidal systems of the PMN. The results obtained from this analysis will increase our knowledge regarding the structural-functional relationships of the gonococcal cell envelope and will advance our understanding of the host and bacterial factors which regulate gonococcal pathogenesis.